TY - JOUR T1 - Stable Respiratory Activity Requires Both P/Q-Type and N-Type Voltage-Gated Calcium Channels JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3633 LP - 3645 DO - 10.1523/JNEUROSCI.6390-11.2013 VL - 33 IS - 8 AU - Henner Koch AU - Sebastien Zanella AU - Gina E. Elsen AU - Lincoln Smith AU - Atsushi Doi AU - Alfredo J. Garcia III AU - Aguan D. Wei AU - Randy Xun AU - Sarah Kirsch AU - Christopher M. Gomez AU - Robert F. Hevner AU - Jan-Marino Ramirez Y1 - 2013/02/20 UR - http://www.jneurosci.org/content/33/8/3633.abstract N2 - P/Q-type voltage-gated calcium channels (Cav2.1) play critical presynaptic and postsynaptic roles throughout the nervous system and have been implicated in a variety of neurological disorders. Here we report that mice with a genetic ablation of the Cav2.1 pore-forming α1A subunit (α1A−/−) encoded by CACNA1a (Jun et al., 1999) suffer during postnatal development from increasing breathing disturbances that lead ultimately to death. Breathing abnormalities include decreased minute ventilation and a specific loss of sighs, which was associated with lung atelectasis. Similar respiratory alterations were preserved in the isolated in vitro brainstem slice preparation containing the pre-Bötzinger complex. The loss of Cav2.1 was associated with an alteration in the functional dependency on N-type calcium channels (Cav2.2). Blocking N-type calcium channels with conotoxin GVIA had only minor effects on respiratory activity in slices from control (CT) littermates, but abolished respiratory activity in all slices from α1A−/− mice. The amplitude of evoked EPSPs was smaller in inspiratory neurons from α1A−/− mice compared with CTs. Conotoxin GVIA abolished all EPSPs in inspiratory neurons from α1A−/− mice, while the EPSP amplitude was reduced by only 30% in CT mice. Moreover, neuromodulation was significantly altered as muscarine abolished respiratory network activity in α1A−/− mice but not in CT mice. We conclude that excitatory synaptic transmission dependent on N-type and P/Q-type calcium channels is required for stable breathing and sighing. In the absence of P/Q-type calcium channels, breathing, sighing, and neuromodulation are severely compromised, leading to early mortality. ER -